PROJECT SUMMARY Background. Substance abuse is largely not addressed in HIV care in South Africa (SA). This is despite the fact that SA has the largest number of people living with HIV/AIDS globally, and that substance abuse is prevalent and associated with worse antiretroviral therapy (ART) adherence. Implementing evidence-based interventions for substance abuse and ART nonadherence in HIV care by paraprofessionals may improve HIV treatment and prevention. Research Strategy. The current study uses a theoretically-driven approach to adapt and evaluate a paraprofessional-delivered intervention for substance abuse and ART nonadherence in HIV care in SA. Three phases include: (1) Qualitative assessment phase of barriers and facilitators to implementation using in-depth individual interviews with patients, providers and staff (n=30); (2) Treatment adaptation phase based upon qualitative analysis in Aim 1; and (3) Randomized pilot hybrid effectiveness-implementation trial1 (n=60) to evaluate the adapted, paraprofessional delivered intervention compared to enhanced standard of care (SOC) over 6 months. Effectiveness outcomes include: (1) ART adherence (real-time wireless electronic monitoring); (2) substance use (urinalysis and self-report); and (3) viral load (exploratory). Implementation outcomes follow recommendations in the field and include feasibility, acceptability, and barriers and facilitators to implementation.2 The K23 lays the groundwork for an R01 to propose a larger-scale trial using clinic-based randomization to evaluate the implementation of the intervention. Training Plan. Coordinated with the research plan, Dr. Magidson will receive mentorship and training to correspond with each aim in the following: (1) implementation science methodology relevant to substance abuse treatment and HIV care in resource-limited global settings; (2) competence for conducting independent, global clinical research; and (3) qualitative analysis. Mentorship. K23 mentors offer complementary expertise central to project aims. Her primary mentor, Dr. Bangsberg, is an expert in ART adherence implementation research in resource-limited global settings, and mentoring K awardees to transition to independent investigators. Her co-mentors combine expertise intervention development for ART adherence and psychiatric comorbidity (Safren), screening for substance abuse in HIV clinic settings in SA (Joska), and developing and evaluating evidence-based interventions for substance use in SA using implementation science and qualitative methods (Myers). This mentorship is supported by a team of consultants who comprise internationally recognized investigators in ART adherence, qualitative analysis, substance abuse and HIV, biostatistics, and implementation research in SA. Candidate. Dr. Magidson has been productive as an early career researcher (with 38 publications, 22 first author, and an F31 and R36 focused on domestic HIV and substance abuse effectiveness research). The K23 would expand her career focus to become an independent investigator with expertise in implementation science for substance abuse and HIV in resource-limited settings.